Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein
Identification and Characterization of Three Novel Nuclear Export Signals in the Influenza A Virus Nucleoprotein
复制标题
甲型流感病毒核蛋白中三种新型核输出信号的鉴定和表征
DOI：
10.1128/jvi.06159-11
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发表时间：
2012-02
影响因子：
5.4
通讯作者：
Bi, Yuhai
中科院分区：
文献类型：
--
作者：
Yu, Maorong;Sun, Lei;Ye, Xin;Gao, George F.;Liu, Wenjun;Liu, Xiaoling;Cao, Shuai;Zhao, Zhendong;Zhang, Ke;Xie, Qing;Chen, Caiwei;Gao, Shengyan;Bi, Yuhai
摘要甲型流感病毒核糖核蛋白（vRNP）的核输出对病毒复制至关重要。作为vRNP的主要成分，核蛋白（NP）单独也可以通过与染色体区域维持1（CRM 1）相互作用而穿梭出细胞核，因此推测其促进vRNP的核输出。在本研究中，NP-NES 1，NES 2和NES 3-三个新的核输出信号（NESs）被确定为负责介导其核输出。NES 3的核输出依赖于CRM 1，而NES 1和NES 2的核输出不依赖于CRM 1。这些NES的失活导致NP的总体核积累。所有三种NP-NES的突变显著损害病毒复制。基于流感病毒NP寡聚体的结构，发现这三种疏水NES存在于寡聚体NP的表面上。功能研究表明，寡聚化也需要核输出的NP。总之，这些结果表明NP的核输出对于病毒复制是重要的，并且依赖于其NES和寡聚化。
ABSTRACT The nuclear export of the influenza A virus ribonucleoprotein (vRNP) is crucial for virus replication. As a major component of the vRNP, nucleoprotein (NP) alone can also be shuttled out of the nucleus by interacting with chromosome region maintenance 1 (CRM1) and is therefore hypothesized to promote the nuclear export of the vRNP. In the present study, three novel nuclear export signals (NESs) of the NP—NES1, NES2, and NES3—were identified as being responsible for mediating its nuclear export. The nuclear export of NES3 was CRM1 dependent, whereas that of NES1 or NES2 was CRM1 independent. Inactivation of these NESs led to an overall nuclear accumulation of NP. Mutation of all three NP-NESs significantly impaired viral replication. Based on structures of influenza virus NP oligomers, these three hydrophobic NESs are found present on the surface of oligomeric NPs. Functional studies indicated that oligomerization is also required for nuclear export of NP. Together, these results suggest that the nuclear export of NP is important for virus replication and relies on its NESs and oligomerization.
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影响因子：
4.4
作者：
J. Yewdell;E. Frank;W. Gerhard
通讯作者：
J. Yewdell;E. Frank;W. Gerhard
影响因子：
64.5
作者：
Fornerod, M;Ohno, M;Mattaj, IW
通讯作者：
Mattaj, IW
影响因子：
3.7
作者：
Li G;Zhang J;Tong X;Liu W;Ye X
通讯作者：
Ye X
DOI：
10.1002/j.1460-2075.1990.tb07871.x
发表时间：
1990-12
期刊：
The EMBO Journal
影响因子：
--
作者：
T. Stegmann;J. M. Whitel;A. Helenius
通讯作者：
T. Stegmann;J. M. Whitel;A. Helenius
影响因子：
21.3
作者：
Pleschka, S;Wolff, T;Ludwig, S
通讯作者：
Ludwig, S